Aggressive behaviour: neurological disorders

Behavioural changes secondary to organic diseases are relatively common and justify a careful clinical examination during a consultation for behavioural problems (Fig. 1).

 In the light of the model proposed by P. Pageat, the diagnosis of a behavioural disorder is a differential diagnosis, not a “hold all” diagnosis when an organic disease cannot be identified. An organic disease should be particularly suspected when:

- a behavioural disorder appears abruptly or evolves rapidly without apparent cause;

- there is rapid exploitation of the aggressive behaviours;

- phobias appear unexpectedly, with no traumatic cause, in an adult dog;

- there is worsening of already present phobias characterized by symptoms that suddenly become “very productive”;

- the animal’s symptoms do not fit into a well-defined clinical picture or there is inconsistency in the origin of the behavioural disorder.

The veterinarian should suspect the presence of an organic disease, whose symptoms mimic a behavioural disorder, when: (i) it is not possible to make a nosographic diagnosis (name the disease), but only a functional one (the presence of a pathological state such as phobia, anxiety, depression, dysthymia and so on); (ii) the symptoms shown by the animal appear to be “inconsistent” with the normal behavioural pattern of the species under examination; and (iii) the symptoms appear “unexpectedly”, with no history of prior behavioural disorders.

In clinical practice, aggressive behaviour in the dog is a non-pathognomonic sign of a disorder of the central nervous system (CNS). The incidence of this sign does, however, appear to be very low. In general, it can be said that increased intracranial pressure in some areas of the cerebrum (frontal zone, temporal area) and pain associated with inflammatory diseases of the meninges can underlie the onset of aggressive behaviour in dogs.

The main neurological disorders implicated are:

• Vascular
• Inflammatory: meningoencephalitis (autoimmune, viral [rabies, pseudorabies, distemper, herpes virus infection, bacterial [tetanus], protozoan [toxoplasmosis, erlichiosis, borreliosis], parasitic [dirofilariosis], mycotic [cryptococcosis, neosporosis]);
• Toxic and endocrine;
• Congenital: hydrocephalus (primary and secondary);·Metabolic and storage;
• Idiopathic;
• Neoplastic;
• Degenerative;
• Epilepsy and convulsive syndromes;
• Head injury;
• Neuropsychiatric disorders.

Structural or metabolic conditions that may underlie behavioural disorders (vitamin D)

• Vascular: non-traumatic vascular disorders are rare in domestic animals. Behavioural manifestations of convulsive crises are common when the ischaemic area includes the pyriform lobe.
• Inflammatory: distemper can be the cause of an extremely localised encephalitis or myelitis in the adult dog. Behavioural manifestations, such as epileptic-like crises or incontinence may be present without any of the other classical signs of this infection.
• Toxic: some compounds administered for therapeutic purposes (for example, antihistamines, cortisones, neuroleptic drugs [acepromazine], anxiolytics [benzodiazepines], arylcyclohexylamines [ketamine, tiletamine] and so on) can be the cause of unwanted behavioural manifestations as a result of their direct action on the CNS.
• Anatomical: abnormal behaviour can appear progressively or acutely in animals with congenital or secondary hydrocephalus. The same is true for some storage diseases.
• Metabolic: metabolic disorders do not, usually, affect the CNS directly, but create imbalances in the normal functioning of the animal, which can have secondary effects on nervous system structures.
• Idiopathic: numerous forms of epilepsy can be confused with behavioural manifestations.
• Neoplastic: behavioural changes are part of the expected clinical picture, particularly when the frontal or prefrontal cortex is involved.
• Degenerative: congenital or idiopathic atrophy is frequently associated with abnormalities of neurotransmitters.

Meningoencephalitis

• Inflammatory diseases are frequent in the neurology clinic and can appear in animals of any age, although puppies and young animals are most susceptible. Autoimmune inflammatory diseases are found more commonly in canine neurology clinics. Pain is the most obvious and consistent clinical sign: it can be severe enough to cause a fast change in the animal’s behaviour (M. Bernardini). The aggressive behaviour can appear precisely because of the pain.
• The aggressive behaviour described in rabies is related to the multifocal localisation of the virus which affects numerous areas of the brain. The pain caused by the inflammatory component of the infection contributes to altering the patient’s behaviour.

Hydrocephalus

• Congenital hydrocephalus: behavioural development is slow and learning difficult, these animals are “behind” other animals of their same age. The animal’s inability to learn correct elimination behaviour is obvious (the animal eliminates when it needs to, wherever it finds itself) as is the state of almost constant avoidance (difficulty in taking the initiative with regards to contact). Animals with congenital hydrocephalus are fairly inactive and do not play much. The disorder is often associated with sensory defects, such as deafness and visual impairment. Aggressive behaviour may develop as a result of the increased intracranial pressure and associated sensory defects. P. Pageat described the occurrence of a dysthymic state in animals with congenital hydrocephalus.
• Acquired hydrocephalus: aggressive behaviour is related to the increased intracranial pressure, particularly of some cerebral areas. P. Pageat described the occurrence of a dysthymic state: the dog’s mood is instable with phases of irritability (characterized by an increased frequency of irritation-elicited aggression) alternating with periods of normality. Inappropriate elimination is intermittent. Insomnia is present with reversal of the normal sleep-wake cycle (the dog sleeps 2 – 3 hours/ 24 hours).

It is important to note that there is no correlation between the severity of the organic lesion and the clinical signs.

Toxic disorders

• Some compounds administered for therapeutic purposes (for example, antihistamines, cortisones, neuroleptic drugs [acepromazine], anxiolytics [benzodiazepines], arylcyclohexylamines [ketamine, tiletamine] and so on) can be the cause of unwanted behavioural manifestations as a result of their direct action on the CNS.
• Antihistamines and cortisones can induce excitation or depression in dogs.
• Anabolic steroids used for the treatment of anorexia/cachexia and frailty have been associated with increases in aggressive reactions (N. H. Dodman).
• Some sedative neuroleptics have a dose-dependent effect: for example, at a low dose, acepromazine is able to promote certain behaviours through a replenishment effect. The molecules bind to D2 pre-synaptic and D3 post-synaptic dopaminergic receptors with an antagonist action (the receptors are blocked) and greater affinity for the D2 receptors. The neuroleptics, initially and if at low doses, bind to the pre-synaptic autoreceptors and, by blocking them, inhibit the process of negative feedback control, thereby increasing the release of dopamine. When the dose of neuroleptics increases, the D2 receptors become saturated and the molecules start to bind to the D3 post-synaptic receptors, blocking the action of dopamine and decreasing transmission. This is the anti-productive action of the neuroleptic. The paradoxical effect is, therefore, due to a dose-differentiated action on dopamine levels.
• Loss of memory (amnesic effect) and marked disinhibition are the main side effects of benzodiazepines. The disinhibition, sometimes violent (see the rebound orexigenic effect), is particularly unwanted in situations of social conflict (in the context of the family) because it can be responsible for unexpected, brutal aggression by the animal (Colangeli – Giussani).

The arylcyclohexylamines stimulate the limbic system and the reticular substance while they depress the activity of the thalamus and cortex. The administration of these compounds, therefore, causes a dissociation between sensory perception and cortical integration. The animal appears to be unconscious, but external stimuli (above all sounds and changes in light) are perceived and trigger emotional responses. After awakening from the anaesthesia, the animal can manifest photophobia and behavioural changes induced by the presence of eidola (visual hallucinations). When the dog is in a peaceful environment, avoidance or aggressive behaviour may occur as a response to any stimulus (P. Pageat).

Neoplasms

• Tumours of the frontal zone and temporal area can cause, among other signs, the onset of aggressive behaviour. From an epidemiological point of view, these disorders are rare in dogs. According to P. Pageat diencephalic tumours (metastases from a primary malignancy in another site) are more common and give a clinical picture of chronic depression (appetite disorders, insomnia with inversion of the sleep-wake cycle, oral exploration with ingestion, loss of initiative).
• The onset of aggressive behaviour can be related to increased intracranial pressure secondary to the neoplasm and to pain caused by a space-filling lesion compressing the surrounding tissues.
• According to P. Pageat, tumours of the cerebral cortex could be an underlying cause of hyper-aggressiveness in the elderly dog. This pathology is characterized by an increased tendency to aggressive acts in dogs over 7 years old. The sequence of aggression loses its original structure because the intimidation phase follows the biting and the phase of contentment is absent.

It is important to note that the severity of the visible neurological problems is not related to the size of the tumour.

Epilepsy and convulsive syndromes 

• Some neurones in the cerebral cortex and subcortical structures have the tendency to activate at a much faster rhythm than normal, producing so-called epileptic discharges. If this phenomenon remains circumscribed, the crisis is focal and the clinical manifestations vary depending on the functions performed by the area involved. The most common simple focal crisis seen in veterinary neurological practice is contraction of a defined group of muscles, since in animals it is impossible to detect clinically the numerous conditions that occur in human medicine (abnormal visual, auditory or taste sensations, pallor, sweating, anxiety, distorted perception of self, etc.) (M. Bernardini).
• Of the various psychomotor crises (complex focal crises characterized by the comtemporaneous presence of motor crises and behavioural alterations), the so-called fly biting syndrome is particularly important. This can affect various breeds of dog, often small ones, but the Cavalier King Charles Spaniel seems to be particularly susceptible. The syndrome is characterized by abrupt movements of the mandible, as if the animal is trying to give a sharp bite at an imaginary object that moves in the air and that the animal continues to fix. It seems exactly as if the animal is trying to catch a moving fly, and hence the name of the syndrome (M. Bernardini).
• In humans epilepsy of the temporal lobe has been associated with two types of aggression: aggression at the time of the epileptic attack or immediately after it and aggression that occurs between one attack and another. During the convulsions and in the period immediately after them, patients can lash out in the air with their hands, feet or objects. This form of aggression seems to be casual and not targeted. The aggressive behaviour that occurs between two attacks can be triggered by insignificant stimuli and the threshold for aggressive rage is lowered. Patients with this form of aggression can manifest symptoms of paranoia, phobias, panic attacks or sexual fetishism between one attack and another. In dogs, the increase in peaks of activity in the temporal lobe has been associated with aggressive behaviour. In subjects with extreme swings of mood, the episodic loss of control due to partial seizures can mimic dominance (hierarchy) aggression. Other behavioural alterations can also be observed in these animals, such as extreme fear, narrow or wide circling and tail-chasing, increased sensitivity to light and noise, hyperactivity, paw- and flank-licking and fly-biting syndrome. The episodic loss of control is usually seen for the first time in puberty or early adulthood and tends to intensify with ageing. The rage syndrome observed in Springer Spaniels is probably due to episodic loss of control. Beaver described a syndrome of mental collapse that seems to produce similar aggressive behaviour (N. H. Dodman).
• The clear majority of convulsions in small animals are generalised attacks (involving all the muscles of the body) from their onset. Aggressive behaviour may appear more frequently in the post-convulsive phase of the crisis, when sensory defects such as amaurosis (blindness of central origin) may occur (M. Bernardini).

Neuropsychiatric disorders

• P. Pageat includes dissociative syndrome among the behavioural disorders that can appear during development. Certain breeds are more predisposed (German Shepherd and Bull Terrier are the most frequently affected breeds) and there are also familial cases. Pageat describes that warning signs of the disorder occur in the pre-pubertal period: females become fearful and show avoidance behaviour, while males become very impulsive. The set of manifestations of the syndrome appears between the pre-pubertal period and 5 years of age. These may include hallucinations characterized by the production of stereotypies such as aggressive predatory behaviour towards an imaginary prey. The aggressive behaviour may be directed towards humans, if they try to distract the dog from its target.  P. Pageat has found that animals with this disorder may have unilateral or bilateral dilatation of the lateral ventricles, hippocampal atrophy and isolated spikes on an electroencephalogram. All this has given rise to a debate between neurologists and behaviouralists on the origin of the disorder and the treatment to use. The dissociative syndrome can be considered an animal model of human schizophrenia.
• P. Pageat includes dysthymia among the behavioural disorders that can appear in adult and elderly animals. Once again, certain breeds are more predisposed (German Shepherd, Bull Terrier, Doberman, and Bichon Frisé are the most frequently affected breeds). It is difficult to establish the origin of this disorder: it seems that the presence of behavioural alterations that appear (and are not treated) during development are a determinant factor. Furthermore, a large percentage of patients with dysthymia have Cushing’s syndrome: however, it has not yet been possible to establish whether the endocrine disorder is primary or secondary to the dysthymia. The animal shows unpredictable changes in mood: in unipolar dysthymia there is a swing from normality to excitation, whereas in the bipolar condition the animal swings from excitation to normality and to depression. During the excitatory phase, the dog appears excessively vigil and excitable and sleeps 6 out of 24 hours, has phases of fixation and often shows irritation-elicited aggression (towards its owners or other dogs). Changes in the diameter of the pupil (mydriasis) indicate the start of the productive phase. A neurological disorder (congenital or acquired hydrocephalus) has been found in some patients with bipolar dysthymia.

Suggested readings

1. BERNARDINI M, Neurologia del cane e del gatto, Poletto editore, 2002, Gaggiano (Mi);
2. COLANGELI R,, GIUSSANI S, Medicina comportamentale del cane e del gatto, Poletto editore, 2005 Gaggiano (Mi);
3. DAMINT S, BEATA C, (2005) Endocrinology and behaviour, About Hierarchy, Behaviour and Internal Medicine ESVCE, Marseille 8 – 9 october;
4. DODDS WJ, (2004) Behavioral issues and thyroiditis: theory and case review. Proceedings American Holistic Veterinary Medical Association;
5. DODMAN NH, SHUSTER L, Farmacologia comportamentale veterinaria, Masson s. p. a., 2000, Milano;
6. FATJO’ J., MANTECA X. (1999) “Problemas de comportamiento en perros y gatos”. Dal: Seminario Iberoamericano de Comportamiento en Perros y Gattos, Univ. de Ciencias Aplicadas y Ambientales (U.D.C.A), Facultad de Ciencias Agropecuarias, Carrera de Medicina Veterinaria - Universtad Autónoma de Barcelona (U.A.B.). 4 e 5 Novembre 1999, Santa Fe de Bogotà, D.C;
7. FERRIERE C, Eduquer un chien sourd, La communication, collection Zoopsychiatrie, 2005, Solal Editeur;
8. GIUSSANI S, Perte de la vision et modifications comportementales chez les carnivores domestiques, Mémoire pour l’obtention du diplome de Vétérinaire Comportementaliste del Ecoles Nationales Vétérinaires, 2002 Nantes;
9. HOPKINS S.G., Schulbert T.A., Hart B.L. (1976) Castration of adult male dogs: effects on roaming, aggression, urine making and mounting;
10. MEGE C, BEAUMONT – GRAFF E, BEATA C, DIAZ T, HABRAN T, MARLOIS N,, MULLER G, Patologia comportamentale del cane, Masson s. p. a ed EV s. r. l.., Milano/ Cremona,  2006 prima edizione;
11. Neilson J.C., Eckstein, R.A., Hart B.L. (1997) Effects of castration on problem behaviors in male dogs with reference to age and duration of behavior. J Am Vet Med Assoc 1997 Jul 15;211(2);
12. O'Farrell V, Peachey E.. Behavioural effects of ovariohysterectomy on bitches. J Small Anim Pract. 1990;.
13. OVERALL KL, La clinica comportamentale del cane e del gatto, C. G. Edizioni Medico Scientifiche s. r. l., Torino, prima edizione italiana;.
14. PAGEAT P, “La patologia comportamentale del cane” – Edizione Le Point Veterinaire Italie Milano 2000;
15. SALMERI, K.R., BLOOMBERG, M.S., SCRUGGS,S.L., SCHILLE, V. (1991) Gonadectomy in immature dogs: effects on skeletal, physical, and behavioural development. J. Am. Vet. Med. Assoc.